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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Platelets of COVID-19 patients display mitochondrial dysfunction, oxidative stress, and energy metabolism failure compatible with cell death
Research and Practice in Thrombosis and Haemostasis, Volume 7, No. 7, Article 102213, Year 2023
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Description
Background: Alterations in platelet function have been implicated in the pathophysiology of COVID-19 since the beginning of the pandemic. While early reports linked hyperactivated platelets to thromboembolic events in COVID-19, subsequent investigations demonstrated hyporeactive platelets with a procoagulant phenotype. Mitochondria are important for energy metabolism and the function of platelets. Objectives: Here, we sought to map the energy metabolism of platelets in a cohort of noncritically ill COVID-19 patients and assess platelet mitochondrial function, activation status, and responsiveness to external stimuli. Methods: We enrolled hospitalized COVID-19 patients and controls between October 2020 and December 2021. Platelets function and metabolism was analyzed by flow cytometry, metabolomics, glucose fluxomics, electron and fluorescence microscopy and western blot. Results: Platelets from COVID-19 patients showed increased phosphatidylserine externalization indicating a procoagulant phenotype and hyporeactivity to ex vivo stimuli, associated with profound mitochondrial dysfunction characterized by mitochondrial depolarization, lower mitochondrial DNA–encoded transcript levels, an altered mitochondrial morphology consistent with increased mitochondrial fission, and increased pyruvate/lactate ratios in platelet supernatants. Metabolic profiling by untargeted metabolomics revealed NADH, NAD+, and ATP among the top decreased metabolites in patients’ platelets, suggestive of energy metabolism failure. Consistently, platelet fluxomics analyses showed a strongly reduced utilization of 13C-glucose in all major energy pathways together with a rerouting of glucose to de novo generation of purine metabolites. Patients’ platelets further showed evidence of oxidative stress, together with increased glutathione oxidation and synthesis. Addition of plasma from COVID-19 patients to normal platelets partially reproduced the phenotype of patients’ platelets and disclosed a temporal relationship between mitochondrial decay and (subsequent) phosphatidylserine exposure and hyporeactivity. Conclusion: These data link energy metabolism failure in platelets from COVID-19 patients with a prothrombotic platelet phenotype with features matching cell death. © 2023 The Authors
Authors & Co-Authors
Léopold, Valentine
Netherlands, Amsterdam
Universiteit Van Amsterdam
France, Paris
Inserm
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
de Brabander, Justin
Netherlands, Amsterdam
Universiteit Van Amsterdam
van Baarle, Frank E.F.P.
Unknown Affiliation
Bogaard, H. J.
Unknown Affiliation
Bonta, Peter I.
Unknown Affiliation
Bos, Lieuwe D.J.
Unknown Affiliation
de Bree, Godelieve J.
Unknown Affiliation
de Bruin, Sanne
Unknown Affiliation
Bugiani, Marianna
Unknown Affiliation
Elbers, Paul W.G.
Unknown Affiliation
Geerlings, Suzanne Eugenie
Unknown Affiliation
Goorhuis, Bram
Unknown Affiliation
Grobusch, Martín Peter
Unknown Affiliation
Hagens, Laura A.
Unknown Affiliation
Harris, Vanessa C.
Unknown Affiliation
Hermans, S. M.
Unknown Affiliation
Heunks, Leo M.A.
Unknown Affiliation
Hollmann, M. Werner
Unknown Affiliation
Horn, Janneke
Unknown Affiliation
Hovius, Joppe Willem R.
Unknown Affiliation
de Jong, Menno Douwe
Unknown Affiliation
Koning, Rutger
Netherlands, Amsterdam
Amsterdam Neuroscience
Lim, Endry H.T.
Unknown Affiliation
Nossent, Esther J.
Unknown Affiliation
Olie, Sabine E.
Netherlands, Amsterdam
Amsterdam Neuroscience
Peters, Edgar J.
Unknown Affiliation
van der Poll, Tom
Netherlands, Amsterdam
Universiteit Van Amsterdam
Schultz, Marcus Josephus
Unknown Affiliation
Sigaloff, Kim Catherina Eve
Unknown Affiliation
Slim, Marleen A.
Unknown Affiliation
Smeele, Patrick J.
Unknown Affiliation
Smit, Marry R.
Unknown Affiliation
Tuinman, Pieter Roel
Unknown Affiliation
van der Valk, Marc
Unknown Affiliation
Veelo, Denise Petra
Unknown Affiliation
Zwinderman, Aeilko Having Koos
Unknown Affiliation
Brouwer, Matthijs C.
Netherlands, Amsterdam
Amsterdam Neuroscience
Wiersinga, Willem Joost
Netherlands, Amsterdam
Universiteit Van Amsterdam
Vlaar, Alexander Petrus Johannes
Unknown Affiliation
van de Beek, Diederik V.D.
Netherlands, Amsterdam
Amsterdam Neuroscience
van der Wel, Nicole Neeltje
Netherlands, Amsterdam
Universiteit Van Amsterdam
van 't Veer, Cornelis
Netherlands, Amsterdam
Universiteit Van Amsterdam
Statistics
Citations: 1
Authors: 42
Affiliations: 5
Identifiers
Doi:
10.1016/j.rpth.2023.102213
ISSN:
24750379
Research Areas
Covid
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cohort Study
Case-Control Study